Histones are basic proteins which are associated with nuclear DNA of eukaryotic cells and in which reversible acetylation of the lysine residues occurs at certain positions of histone molecules. It is considered that such acetylation of histone proteins is involved in formation of high-order structures of chromatin, which plays a role in regulation of expression of genetic information in conjunction with non-histone proteins.
Regulation of transcription is a critical factor in differentiation, proliferation and death of cells and such cellular processes are controlled by a degree of acetylation of nucleosomal histones. Histone deacetylase (hereinafter, referred to as HDAC) and histone acetyltransferase (hereinafter, referred to as HAT) are related to acetylation of histone which plays a role to regulate gene expression. In particular, among a variety of nuclear processes, regulation of transcription is crucial for regulation of a cell cycle, and occurrence of disorders or dysfunctions in cell cycle regulation may result in diseases such as cancers and inflammation.
There has recently been found the fact that an HDAC inhibitor inhibits growth of various types of cancer cells or induces apoptosis thereof (Bandyopadhyay D et al. (2004) Cancer Research, 64, 7706-7710). Numerous HDAC inhibitors are currently undergoing clinical testing on patients, for treatment purpose of blood cancers and solid cancers. In addition, it was also reported that the HDAC inhibitor is involved in cell proliferation and differentiation, and therefore exhibits anti-autoimmune properties against autoimmune diseases such as arthritis, lupus, and the like diseases, and has neuroprotective and anti-inflammatory effects (Spira et al. (2003) Current Opinion in Pharmacology, 3, 338-343, Marks et al. (2001) Nature review cancer, 1, 194-202). Further, the recently published article has reported the possibility that the HDAC inhibitor may exert therapeutic effects on obesity or diabetes (Picard et al. (2004), Nature, 429, 771-776). Additionally, the HDAC inhibitor, due to anti-cancer effects thereof, may be utilized as a sensitizing agent in chemotherapy or radiotherapy. Recently, it is known that the HDAC inhibitor may be used in treatments via virus-induction such as in HIV (Cohen J et al. (2005), Science, 12, 999-1000).